The overall objective is to study models of renal disease in order to provide an understanding of the basic mechanisms of autoimmune diseases and inflammation in man. In this proposed study we will examine the pathogenesis of autoimmune renal tubulointerstitial disease (RTD) in guinea pigs which has led to the discovery of similar renal disease in man. Our observations point towards a unique type of inflammatory reaction which involves anti-tubular basement membrane (TBM) autoantibodies, the alternative pathway of complement, and radiosensitive as well as radioresistant mononuclear cells. Our observations suggest a new hypothesis for this inflammatory reaction: complement-receptor lymphocytes accumulate in the target tissue and are activated by complement to release factors which mediate the influx of macrophages. We will identify these infiltrating cells and their functional characteristics. We will determine if C3b or C3d-receptor mononuclear cells are capable of accumulating in the target tissue by examining the functional role of B-lymphocytes, macrophages, and the complement components in the target tissue. These studies will be extended to the mouse because we have been able to induce anti-TBM autoantibodies in mice similar to those found in the guinea pig. We have also observed the possible spontaneous production of anti-TBM autoantibodies in some (NZB/NZW)F1 mice, and have described a new spontaneous renal tubulointerstitial disease in CBA/J mice which may be inheritable and have an immunological basis. Thus, the combined effort of these interrelated studies will provide new information for the basic understanding of autoimmunity and inflammation.